PIGN spatiotemporally regulates the spindle assembly checkpoint proteins in leukemia transformation and progression

Sci Rep. 2021 Sep 24;11(1):19022. doi: 10.1038/s41598-021-98218-y.

Abstract

Phosphatidylinositol glycan anchor biosynthesis class N (PIGN) has been linked to the suppression of chromosomal instability. The spindle assembly checkpoint complex is responsible for proper chromosome segregation during mitosis to prevent chromosomal instability. In this study, the novel role of PIGN as a regulator of the spindle assembly checkpoint was unveiled in leukemic patient cells and cell lines. Transient downregulation or ablation of PIGN resulted in impaired mitotic checkpoint activation due to the dysregulated expression of spindle assembly checkpoint-related proteins including MAD1, MAD2, BUBR1, and MPS1. Moreover, ectopic overexpression of PIGN restored the expression of MAD2. PIGN regulated the spindle assembly checkpoint by forming a complex with the spindle assembly checkpoint proteins MAD1, MAD2, and the mitotic kinase MPS1. Thus, PIGN could play a vital role in the spindle assembly checkpoint to suppress chromosomal instability associated with leukemic transformation and progression.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Cell Transformation, Neoplastic / genetics*
  • Chromosomal Instability / genetics*
  • Disease Progression
  • Gene Expression
  • HL-60 Cells
  • Humans
  • K562 Cells
  • Leukemia / pathology*
  • Mad2 Proteins / genetics
  • Mad2 Proteins / metabolism
  • Phosphotransferases / genetics
  • Phosphotransferases / metabolism
  • Phosphotransferases / physiology*
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism
  • Spindle Apparatus / metabolism*

Substances

  • Cell Cycle Proteins
  • MAD1L1 protein, human
  • MAD2L1 protein, human
  • Mad2 Proteins
  • PIGN protein, human
  • Phosphotransferases
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases
  • TTK protein, human